This project aims to define biochemical effects of antineoplastic nitrosoureas and the relation between certain of these effects and cell survival. Chloroethyl nitrosoureas decompose quickly, forming a product capable of alkylation and cross-linking of DNA. Many nitrosoureas also form a strongly carbamoylating isocyanate decomposition product capable of inhibiting DNA repair. The biologic consequences of this repair-inhibiting capability now require careful definition. Nitrosoureas are to be compared for their effects on DNA structure with regard to: a) formation and removal of cross-links, and b) production and repair of strand breaks. Nitrosoureas will also be compared for their ability to produce more-than-additive cytotoxicity when given in combination with another DNA-damaging agent -- either a conventional alkylating agent, or x-ray. Special attention will focus on the question of whether enhancement of the cytotoxic effects of a DNA-damaging agent is a function of the nitrosourea's ability to inhibit repair.